Norvaline Reduces Blood Pressure and Induces Diuresis in Rats with Inherited Stress-Induced Arterial Hypertension.

Growing evidence suggests that increased arginase activity affects vital bioprocesses in various systems and universally mediates the pathogenesis of numerous metabolic diseases. The adverse effects of arginase are associated with a severe decline in L-arginine bioavailability, which leads to nitric oxide synthase substrate insufficiency, uncoupling, and, eventually, superoxide anion generation and substantial reduction of nitric oxide (NO) synthesis. In cooperation, it contributes to chronic oxidative stress and endothelial dysfunction, which might lead to hypertension and atherosclerosis. Recent preclinical investigations point arginase as a promising therapeutic target in ameliorating metabolic and vascular dysfunctions. In the present study, adult rats with inherited stress-induced arterial hypertension (ISIAH) were used as a model of hypertension. Wistar rats served as normotensive controls. Experimental animals were intraperitoneally administered for seven days with nonproteinogenic amino acid L-norvaline (30 mg/kg/day), which is a potent arginase inhibitor, or with the vehicle. Blood pressure (BP), body weight, and diuresis were monitored. The changes in blood and urine levels of creatinine, urea, and NO metabolites were analyzed. We observed a significant decline in BP and induced diuresis in ISIAH rats following the treatment. The same procedure did not affect the BP of control animals. Remarkably, the treatment had no influence upon glomerular filtration rate in two experimental groups, just like the daily excretion of creatinine and urea. Conversely, NO metabolite levels were amplified in normotonic but not in hypertensive rats following the treatment. The data indicate that L-norvaline is a potential antihypertensive agent and deserves to be clinically investigated. Moreover, we suggest that changes in blood and urine are causally related to the effect of L-norvaline upon BP regulation.

Methylated arginine analogues: their potential role in atherosclerosis and cognition using the poloxamer-407-induced mouse model of dyslipidemia.

An experimental mouse model of dyslipidemia and atherosclerosis was utilized to study the generation of methylarginines in vivo, as well as any potential behavioral changes in mice associated with the production of excess methylarginines. Following 14 weeks of poloxamer 407 treatment, mice developed atherosclerosis and the plasma concentrations of monomethylarginine and asymmetric dimethylarginine were found to be significantly greater than corresponding concentrations in control mice. This finding may have contributed to the development of aortic atherosclerotic lesions in poloxamer-treated mice by interfering with nitric oxide availability and, hence, normal function of vascular endothelium. Poloxamer-407-treated mice also showed a significant decrease in locomotor and exploratory activity, together with signs of emotional stress and anxiety relative to controls. Passive avoidance testing to assess learning and memory provided suggestive evidence that poloxamer-treated mice could potentially be characterized as having undergone a disruption in the process of forgetting about an aversive event, specifically, a foot shock, when compared with control mice. Thus, it is also suggested that the increase in both plasma monomethylarginine and asymmetric dimethylarginine in poloxamer-407-treated mice may somehow influence learning and memory, because endothelial dysfunction caused by reduced nitric oxide availability has been hypothesized to negatively influence cognitive function.

Cardioprotective effect of resveratrol and resveratroloside.

Cardioprotective effect of resveratrol and resveratroloside was determined in ischemia-reperfusion experiments on rats. It was found that single intraperitoneal administration of any compound (10 mg/kg) followed by 30-min ischemia and 120-min reperfusion resulted in statistically significant decrease of myocardial infarct area (55.0±4.0% for control group; 40.7±4.4% for the group 1 received resveratrol; 41.6±4.8% for the group 2 received resveratroloside). The cardioprotective effect of resveratroloside was detected for the first time.

The Haemonetics Cell Saver 5 washing properties: effect of different washing pump and centrifuge speeds.

This study evaluated the effect of different washing and centrifuge rates of the Cell Saver 5 on the quality of processed autologous blood. Autologous blood was washed with 1000 ml of sterile normal saline at centrifuge speed of 5650 revolutions per minute (rpm) (group I) or 4350 rpm (group II) with different washing pump speeds--500, 800 and 1000 ml/min. Hemoglobin, free hemoglobin, hematocrit, erythrocytes, leukocytes, platelets, and protein were measured before and after processing. The highest values of hemoglobin, hematocrit and erythrocytes were achieved using 800 and 1000 ml/min pump speeds in group I and 500 ml/min speed in group II. Red blood cells concentration was higher in group I. There were no significant changes of free hemoglobin removal within group I. In group II the lowest free hemoglobin was achieved when 1000 ml/min rate was used. Platelets and protein did not depend on wash pump speeds in both groups. Platelet recovery in group I was higher than in group II at all washing pump speeds. Leukocytes were not adequately removed at all pump speeds. The Cell Saver 5 produces optimum results when the high wash pump speeds (800 and 1000 ml/min) and standard centrifuge speed are used.